Azacycloalkylalkanoyl pseudotetrapeptides, as exemplified by N-[N-[N-(4-piperdin-4-yl)butanoyl)-N-ethylglycyl]-(L)-aspartyl]-(L)-.beta. -cyclohexyl-alanine amide, have antithrombotic activity, including the inhibition of platelet aggregation and thrombus formation in mammals, and are useful in the prevention and treatment of thrombosis associated with disease states such as myocardial infarction, stroke, peripheral arterial disease and disseminated intravascular coagulation. See PCT Patent Application Publication No. WO95/10295.
These pseudotetrapeptides have heretofore been prepared by sequential synthesis from the C-terminal amino acid using standard solid phase or solution phase peptide synthesis procedures. However, sequential coupling of amino acids is less desirable for the production of bulk drug as it constrains manufacturing to a linear schedule.
Thus, an alternative preparative approach to the pseudotetrapeptides is needed. Such an approach should substantially increase production versatility and efficiency. A convergent approach should provide for specialized modifications of the pseudotetrapeptide by performing specialized chemistry on one of the synthons rather than on the whole pseudotetrapeptide, and should provide for the simultaneous preparation of a number of pseudotetrapeptide analogs.